Patent FR-2800737-A1 (FR)
Title: New heterocyclic amine compounds have calpain inhibiting and reactive oxygen species capturing activity, useful for treatment of inflammatory and immunological disorders
Inventor: AUVIN SERGE
IPC: A61P35/00
Filed: 1999-11-05
Abstract: Heterocyclic amine compounds (I) are new. Heterocyclic amine compounds of formula (I), their enantiomers, diastereoisomers, and racemic forms, are new. Het = heterocyclyl; R<1> = -OR<3>, SR<3>, oxy or a cyclic acetal; R<3> = H or alkylcarbonyl, arylcarbonyl, or aralkylcarbonyl (all optionally alkyl or aryl substituted by alkyl, OH, alkoxy, nitro, CN, halo or NR<4>R<5>; R<4>, R<5> = H or alkyl; or NR<4>R<5> = optionally substituted heterocycle; R<2> = H, alkyl, aralkyl, or aryl (optionally substituted by 1 or more OR<6>, NR<7>R<8>, halo, CN, nitro or alkyl); R<6>-R<8> = H, alkyl, aryl, aralkyl, alkylcarbonyl or arylalkylcarbonyl; A = a group of formula (i)-(v); R<9>-R<13>  = H, halo, OH, alkyl, alkoxy, CN, NO2 or NR<16>R<16>; R<15>, R<16> = H, alkyl or COR<17>; or NR<15>R<16> = optionally substituted heterocycle; R<17> = H, alkyl, alkoxy or NR<18>R<19>; R<14> = H, alkyl or COR<20>; R<20> = H, alkyl, alkoxy or NR<21>R<22>; W = absent, bond, O, S, NH or N-alkyl; R<24>-R<26> = H, halo, OH, SH, S-alkyl, alkyl, alkenyl, alkoxy or  NR<28>R<29>; R<28>, R<29> = H, alkyl or COR<30>; or R<30> = H, alkyl, alkoxy or NR<31>R<32>; R<18>, R<19>, R<21>, R<22>, R<31>, R<32> = H or alkyl; or NR<18>R<19>, NR<21>R<22>, NR<28>R<29>, NR<31>R<32> = optionally substituted heterocycle; Q = OR<33>, SR<33>, NR<34>R<35> or aryl (optionally substituted by 1 or more halo, OH, alkyl, alkoxy, CN, nitro or NR<15>R<16>); R<33> = H or alkyl; R<34>, R<35> = H, alkyl or CO-alkyl; or NR<34>R<35> = optionally substituted heterocycle; R<37> = H, alkyl or aralkyl; T = methylene or ethylene; R<38> = H, alkyl, aralkyl (aryl group optionally substituted by 1 or more OH, alkyl, halo, nitro, alkoxy or NR<39>R<40>), or -(CH2)q-NR<39>R<40>; R<39>, R<40> = H, alkyl, or COR<41>; or NR<39>R<40> = optionally substituted heterocycle; R<41> = H, alkyl, alkoxy or NR<42>R<43>; R<42>, R<43> = H or alkyl; or NR<42>R<43> = optionally substituted heterocycle; m = 1-2; R<44> = H, OH, alkyl or alkoxy; X = -(CH2)n-, -(CH2)n-CO-, N(R<45>)-CO-(CH2)n-CO-, N(R<45>)-CO-D-CO-, -CH=CH-(CH2)n-CO-, N(R<45>)-CO-C(R<46>R<47>)-CO-, N(R<45>)-(CH2)n-CO-, CO- N(R<45>)- C(R<46>R<47>)-CO-, O-(CH2)n-CO-, or -S-(CH2)n-CO-; D = phenylene (optionally substituted by alkyl, alkoxy, OH, nitro, halo or CN); R<45> = H or alkyl; R<46>, R<47> = H, alkyl, or aralkyl (aryl group optionally substituted by 1 or more OH, halo, nitro, alkyl, alkoxy or NR<48>R<49>); R<48>, R<49> = H, alkyl or COR50; or NR<48>R<49> = optionally substituted heterocycle; R<50> = H, alkyl, alkoxy or NR<51>R<52>; R<51>, R<52> = H or alkyl; or NR<51>R<52> = optionally substituted heterocycle; n = 0-6; Y = -(CH2)p-, C(R<53>R<54>)-(CH2)p-, or C(R<53>R<54>)-CO-; R<53>, R<54> = H, alkyl or aralkyl (aryl group optionally substituted by 1 or more OH, halo, nitro, alkyl, alkoxy or NR<55>R<56>); R<55>, R<56> = H, alkyl or COR<57>; or NR<55>R<56> = optionally substituted heterocycle; R<57> = H, alkyl, alkoxy or NR<58>R<59>; R<58>, R<59> = H or alkyl; or NR<58>R<59> = optionally substituted heterocycle; and p = 0-6; provided that when Het = tetrahydrofuran or tetrahydropyran, R<1> = OH, R<2> = H and Y = bond, then X is not -CO-NH-CH2-CO-.